pituitrin and Ventricular-Dysfunction--Left

The left atrium plays an important role in the maintenance of cardiovascular and neurohumoral homeostasis in heart failure. However, with progressive left ventricular dysfunction, left atrial (LA) dilation and mechanical failure develop, which frequently culminate in atrial fibrillation. Moreover, LA mechanical failure is accompanied by LA endocrine failure [deficient atrial natriuretic peptide (ANP) processing-synthesis/development of ANP resistance) and LA regulatory failure (dominance of sympathetic nervous system excitatory mechanisms, excessive vasopressin release) contributing to neurohumoral overactivity, vasoconstriction, and volume overload (global LA failure). The purpose of the present review is to describe the characteristics and emphasize the clinical significance of global LA failure in patients with heart failure.

Topics: Atrial Fibrillation; Atrial Function, Left; Atrial Natriuretic Factor; Heart Atria; Heart Failure; Humans; Sympathetic Nervous System; Vasoconstriction; Vasopressins; Ventricular Dysfunction, Left

In the course of cardiac diseases, various neuruhomonal systems in the plasma are activated. So far there have been only isolated results of investigations about the functional state of central neuropeptide systems in cardiac diseases and, in particular, in heart failure. We investigated, therefore, the central vasopressinergic system, an important neuropeptide system in cardiocirculatory regulation in a model of myocardial hypertrophy and left ventricular dysfunction, a model of supravalvular aortic stenosis. In addition to increased vasopressin concentrations in plasma, central vasopressin is also altered in this model. A differential stimulation of vasopressin in the hypothalamic areas and in the areas of the brain stem that are involved in central cardiocirculatory regulation was detected. Reduced vasopressin concentrations in the locus coeruleus, an important regulatory area of sympathetic nervous activity, suggest a central regulatory mechanism through which stimulation of the sympathetic nervous activity can be prevented. Our investigations showed that non-osmotic factors like the baroreceptor reflex and angiotensin II, are important stimuli of the vasopressinergic system. We were also able to show that the central vasopressinergic system in rats with experimental heart failure and myocardial hypertrophy is inhibited by treatment with an ACE inhibitor and AT1 receptor antagonist. As seen with autoradiography, this effect is mediated by a central effect of the drugs. Research into central regulatory mechanisms in cardiovascular diseases is, on the one hand, of crucial importance to our understanding of complex pathophysiological processes, and on the other hand, it serves the development of new therapeutic approaches with the goal of influencing these mechanisms directly pharmacologically and for the elucidation of central, currently unknown effects of cardiovascular drugs.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antidiuretic Hormone Receptor Antagonists; Disease Models, Animal; Hypertrophy, Left Ventricular; Vasopressins; Ventricular Dysfunction, Left

In the early phase of asymptomatic left ventricular dysfunction, neurohumoral systems are activated and are closely associated with the deterioration of left ventricular function and the progression into symptomatic heart failure. Congestive cardiac failure is characterized by an increasing activation of the sympathetic nerve activity, the renin angiotensin aldosterone system, vasopressin and endothelin. Together with a reduced endothelial formation of NO, the activation of neurohumoral systems leads to vaso-construction and retention of sodium and water, and by this, to a deterioration of cardiac function. On the other side, systems are activated like prostaglandins, ANP, BNP, dopamine and bradykinin, which act as vasodilators and increase natriuresis and diuresis. In the early phase of cardiac failure, natriuretic and vasodilator mechanisms are able to counteract vasoconstrictor factors, preventing by this unfavorable effects on left ventricular function.

Topics: Animals; Atrial Natriuretic Factor; Endothelins; Heart Failure; Humans; Neurotransmitter Agents; Nitric Oxide; Renin-Angiotensin System; Sympathetic Nervous System; Vasomotor System; Vasopressins; Ventricular Dysfunction, Left

Levosimendan is a new calcium sensitizer with inodilatory properties. There is growing clinical experience with levosimendan given to cardiac surgical patients. The aim of this report was to evaluate the effects of perioperative use of levosimendan in surgical patients with high perioperative risk, compromised left ventricular (LV) function, or difficulties in weaning from cardiopulmonary bypass (CPB).. Case series.. Single-institution, university hospital.. Patients undergoing cardiac surgery.. Sixteen cardiac surgical patients received levosimendan infusion with a maximum duration of 29 hours. Eight were initiated preoperatively and 8 postoperatively. Coronary artery disease was the main operative indication in 10 of 16 cases, and 75% of the patients were high-risk patients.. Continuous levosimendan infusion increased cardiac index significantly in both groups compared with preoperative baseline. Pulmonary capillary wedge pressure and systolic blood pressure did not change significantly. Norepinephrine and epinephrine were the most common concomitant vasoactive medications. Most importantly, weaning from CPB was successful in all patients even after failure to wean the patient with catecholamines. One high-risk patient in the preoperative group and 2 patients in the postoperative group died in the hospital. Another patient died during the 1-year follow-up.. Levosimendan can be used for postoperative rescue therapy for patients difficult to wean from CPB. Also, elective preoperative initiation of levosimendan seems applicable to patients with high perioperative risk or compromised LV function.

Topics: Aged; Anti-Arrhythmia Agents; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Coronary Artery Disease; Epinephrine; Female; Follow-Up Studies; Hemodynamics; Humans; Hydrazones; Male; Milrinone; Norepinephrine; Postoperative Care; Preoperative Care; Pyridazines; Risk Factors; Simendan; Time Factors; Vasoconstrictor Agents; Vasodilator Agents; Vasopressins; Ventricular Dysfunction, Left

Vasopressin, used as a catecholamine adjunct, is a vasoconstrictor that may be detrimental in some hemodynamic profiles, particularly left ventricular (LV) systolic dysfunction. This study tested the hypothesis that echocardiographic parameters differ between patients with a hemodynamic response after vasopressin initiation and those without a response.. This retrospective, single-center, cross-sectional study included adults with septic shock receiving catecholamines and vasopressin with an echocardiogram performed after shock onset but before vasopressin initiation. Patients were grouped by hemodynamic response, defined as decreased catecholamine dosage with mean arterial pressure ≥ 65 mmHg six hours after vasopressin initiation, with echocardiographic parameters compared. LV systolic dysfunction was defined as LV ejection fraction (LVEF) <45%.. Of 129 included patients, 72 (56%) were hemodynamic responders. Hemodynamic responders, versus non-responders, had higher LVEF (61% [55%,68%] vs. 55% [40%,65%]; p = 0.02) and less-frequent LV systolic dysfunction (absolute difference  -16%; 95% CI -30%,-2%). Higher LVEF was associated with higher odds of hemodynamic response (for each LVEF 10%, response OR 1.32; 95% CI 1.04-1.68). Patients with LV systolic dysfunction, versus without LV systolic dysfunction, had higher mortality risk (HR(t) = e. Pre-drug echocardiographic profiles differed in hemodynamic responders after vasopressin initiation versus non-responders.

Topics: Adult; Catecholamines; Cross-Sectional Studies; Echocardiography; Hemodynamics; Humans; Retrospective Studies; Shock, Septic; Vasoconstrictor Agents; Vasopressins; Ventricular Dysfunction, Left

Postoperative vasoplegic shock after cardiac surgery seems to be a frequent complication with poor outcomes. We hypothesized that vasopressin may increase the risk of poor outcomes in patients with preoperative Left Ventricular Dysfunction (pLVD) rather than norepinephrine. The aim of this study was to assess whether vasopressin is superior to norepinephrine to improve outcomes in patients with pLVD after cardiac surgery.. This retrospective cohort study included 1,156 patients with postoperative vasoplegic shock (mean arterial pressure <65 mmHg resistant to fluid challenge and cardiac index >2.20 L/min m) and pLVD (left ventricular ejection fraction ≤35%, left ventricular end-diastolic diameter ≥60 mm, New York Heart Association ≥III) from 2007 to 2017. To address any indicated biases, we derived a propensity score predicting the functions of vasopressin (0.02-0.07 U/min) and norepinephrine (10-60 μg/min) on postoperative vasoplegic shock. The primary outcomes were 30-day mortality, mechanical ventilation more than 48 h, cardiac reoperation, extracorporeal membrane oxygenation, stroke, and acute kidney injury, whereas the secondary outcomes included infection, septic shock, atrial fibrillation and ventricular arrhythmias.. There were 338 patients (169 vasopressin and169 norepinephrine) with a similar risk profile in propensity score-matched cohort. In propensity-matched patients, the primary outcomes of vasopressin and norepinephrine showed no significant difference (50.89% vs. 58.58%, P = 0.155). However, compared with norepinephrine, secondary outcomes of vasopressin were increased due to the high rate of atrial fibrillation (11.83% vs. 20.12%, P = 0.038) and ventricular arrhythmias (14.20% vs. 24.85%, P = 0.014).. Compared with norepinephrine, vasopressin could not improve the postoperative outcomes in patients with pLVD after cardiac surgery. Vasopressin should be cautious to be used as a first-line vasopressor agent in postcardiac vasoplegic shock.

Topics: Aged; Cardiac Surgical Procedures; Female; Humans; Male; Middle Aged; Norepinephrine; Propensity Score; Retrospective Studies; Shock, Septic; Vasoconstrictor Agents; Vasopressins; Ventricular Dysfunction, Left

Acute myocardial infarction (AMI) is associated with left ventricular (LV) dysfunction and clinical heart failure. Arginine vasopressin is elevated in heart failure and the C-terminal of provasopressin (Copeptin) is associated with adverse outcome post-AMI. The aim of this study was to describe the association between Copeptin with LV dysfunction, volumes, and remodeling and clinical heart failure post-AMI.. We studied 274 subjects with AMI. Copeptin was measured from plasma at discharge and subjects underwent echocardiography at discharge and follow-up (median 155 days). Subjects were followed for clinical heart failure for a median of 381 days. Remodeling was assessed as the change (Delta) in LV volumes between echo examinations. Copeptin correlated directly with wall motion index score (WMIS) and inversely with LV ejection fraction (LVEF) at discharge (WMIS, r=0.276, P < .001; LVEF, r=-0.188, P=.03) and follow-up (WMIS, r=0.244, P < .001; LVEF, r=-0.270, P < .001) and with ventricular volumes at follow-up (LVEDV, r=0.215, P=.002; LVESV, r=0.299, P < .001). Copeptin was associated with ventricular remodeling; DeltaEDV; r=0.171, P=0.015, DeltaESV; r=0.186, P=.008. Subjects with increasing LVESV had higher levels of Copeptin (median 6.30 vs. 5.75 pmol/L, P=.012). Subjects with clinical heart failure (n=30) during follow-up had higher Copeptin before discharge (median 13.55 vs. 5.80, P < .001). In a Cox proportional hazards model, Copeptin retained association with clinical heart failure. Kaplan-Meier assessment revealed increased risk in subjects with Copeptin >6.31 pmol/L.. Copeptin is associated with LV dysfunction, volumes, and remodeling and clinical heart failure post-AMI. Measurement of Copeptin may provide prognostic information and the AVP system may be a therapeutic target in post-MI LV dysfunction.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Female; Follow-Up Studies; Glycopeptides; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Survival Rate; Vasopressins; Ventricular Dysfunction, Left; Ventricular Remodeling

Left ventricular end-diastolic pressure (LVEDP) during exercise workload is an important parameter to guide an exercise prescription for patients with cardiovascular disease. Plasma levels of neuro-hormonal factors can be used as a reflection of real-time LVEDP, but its utility is limited by its short half-life. By contrast, the N-terminal fragment of pro-ANP (NT-ANP) has a longer half-life of 1 h.. To determine whether plasma NT-ANP levels at 30 min after exercise can be used as a marker of LVEDP during peak exercise workload in patients with previous myocardial infarction.. Twenty patients with a previous history of myocardial infarction.. Cardiopulmonary exercise test was performed to determine peak VO(2) and anaerobic threshold. Plasma levels of ANP, BNP, NT-ANP, vasopressin and plasma catecholamine were measured at rest, maximum exercise, and 30 min after exercise (recovery).. With the exception of NT-ANP, the levels of each of neuro-hormonal factors peaked at maximum exercise and returned to baseline at recovery. By contrast, NT-ANP levels also increased at peak exercise but remained elevated at 30 min after exercise. Furthermore, NT-ANP levels at recovery correlated with ANP levels at maximum exercise (p<0.01, R=0.75), left ventricular ejection fraction (p<0.02, R=-0.54) and left ventricular systolic dimension (p<0.015, R=0.50).. Plasma NT-ANP levels at 30 min after exercise reflect ANP levels at maximum exercise and left ventricular overload during exercise. These data indicate that plasma NT-ANP after exercise may be a useful parameter to guide prescription of cardiac rehabilitation.

Topics: Aged; Atrial Natriuretic Factor; Blood Pressure; Catecholamines; Exercise; Female; Half-Life; Humans; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Oxygen Consumption; Peptide Fragments; Protein Precursors; Time Factors; Vasopressins; Ventricular Dysfunction, Left

Clinical results of the Maze procedure for treatment of atrial fibrillation (AF) are excellent, suggesting improved ventricular function after restoring sinus rhythm. However, long-term corresponding effects on the release of cardiac natriuretic peptides and other vasoactive hormones are incompletely investigated after isolated Maze surgery.. Plasma levels of brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), antidiuretic hormone, aldosterone, and angiotensin II were measured in 15 patients (mean age, 52 +/- 11 years) undergoing isolated surgical Maze (III) procedures for medically refractory AF, preoperatively and 6 months postoperatively. At the time of blood sampling, hemodynamic correlates were obtained at baseline and after 6 and 12 minutes of rapid ventricular pacing at 150 stimulations/minute.. All patients were free of AF at 6-month follow-up. The measured plasma levels of BNP, ANP, and angiotensin II were all significantly lower (p = 0.03) late after the isolated Maze procedure. Cardiac output was significantly higher postoperatively (p < 0.01). Other hemodynamic values and left atrial size were unchanged after surgery. Ventricular pacing caused almost identical hemodynamic changes in atrial pressures before and late after surgery, but the associated plasma ANP response was significantly attenuated postoperatively (p < 0.001).. Levels of cardiac natriuretic peptides and angiotensin II as markers of ventricular function are improved in the long term after clinically successful isolated Maze procedures. ANP response to hemodynamic challenge by ventricular pacing was attenuated postoperatively, possibly due to atrial scarring.

Topics: Adult; Aged; Aldosterone; Angiotensin II; Atrial Fibrillation; Atrial Natriuretic Factor; Chronic Disease; Cryosurgery; Female; Follow-Up Studies; Hemodynamics; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neurotransmitter Agents; Postoperative Complications; Vasopressins; Ventricular Dysfunction, Left; Ventricular Function, Left

Impaired regulation of salt and water balance in left ventricular dysfunction and heart failure can lead to pulmonary and peripheral edema and hyponatremia. Previous studies of disordered water regulation in heart failure have used models of low cardiac output with normal cardiac function (e.g., inferior vena cava ligation). We investigated thirst and vasopressin (AVP) secretion in a rat myocardial infarction model of chronic left ventricular dysfunction/heart failure in response to a 24-h water deprivation period. Thirst (implied from water drunk), hematocrit, plasma renin activity, and plasma AVP concentrations increased with water deprivation vs. ad libitum water access. Thirst and plasma AVP concentrations were significantly positively correlated with infarct size after 24-h water deprivation but not under ad libitum water access conditions. The mechanism by which this occurs is unclear but could involve increased osmoreceptor sensitivity, altered stimulation of baroreceptors, the renin-angiotensin system, or altered central neural control.

Topics: Animals; Body Weight; Disease Models, Animal; Heart Failure; Myocardial Infarction; Organ Size; Rats; Rats, Sprague-Dawley; Thirst; Vasopressins; Ventricular Dysfunction, Left; Water Deprivation; Water-Electrolyte Balance

The rapid induction of heat shock proteins (HSPs) by cardiac overload has been shown using in vivo models and it is assumed that HSPs are involved in myocardial protection against cardiac overload. However, the mechanisms for the induction of heat shock response by cardiac overload remain unclear. We examined whether increased preload as mechanical stress directly induces heat shock gene expression.. Rat hearts were isolated and perfused with Krebs-Henseleit buffer by the Langendorff method. Whole-cell extracts were prepared for gel mobility shift assay using oligonucleotides containing the heat shock element. We examined the induction of the DNA-binding activity of heat shock transcription factor (HSF), by which the transcription of heat shock genes is mainly regulated, during increased preload of left ventricle (LV) or perfusion with the buffer containing epinephrine, norepinephrine, angiotensin II, or vasopressin.. In preloaded hearts, with LVEDP of both 30 and 50 mmHg, the DNA-binding activity of HSF1 was detected at 10 min, and increased at 20 and 60 min. At any time point, the activity with LVEDP of 50 mmHg was stronger than that with LVEDP of 30 mmHg. However, none of these hypertensive agents activated the DNA-binding activities of HSF. In afterloaded hearts, with the perfusion of norepinephrine, the activation of HSF was not induced.. Our findings demonstrate that increased preload as mechanical stress directly induces the activation of HSF1 in the LV-overloaded heart.

Topics: Angiotensin II; Animals; Cardiomegaly; DNA-Binding Proteins; Epinephrine; Gene Expression Regulation; Heat Shock Transcription Factors; Heat-Shock Proteins; Hemodynamics; Male; Norepinephrine; Organ Culture Techniques; Rats; Rats, Sprague-Dawley; Stress, Mechanical; Transcription Factors; Vasopressins; Ventricular Dysfunction, Left

Experimental myocardial infarction is a model of cardiac overload in which part of the cardiac muscle is removed. The resulting left ventricle insufficiency depends on the size of the infarct and time. The infarcted area remodels, due to proteolytic activity of inflammatory cells and collagenogenesis from fibroblast activity. The phenotype of the residual healthy cardiac muscle undergoes modification, and there are peripheral vascular changes which are partly dependent on the activation of pressor systems and/or inactivation of dilator systems. The changes are proportional to the infarct size at any given time after induction of the model. The degree of right ventricular hypertrophy and the drop in arterial pressure are upstream and downstream markers of the loss of left ventricular function and therefore indicate the extent of the remodelling. The increase of type V3isomyosin, the amount of subendocardial collagen, and the biosynthesis, storage and secretion of atrial natriuretic factor (ANF) are all proportional to the infarct size and the degree of cardiac overload. The level of urinary cGMP is also correlated with infarct size. These indices show ventricular remodelling, increased stress and energy restriction of the residual healthy cardiac muscle. The activation of peripheral pressor systems also depends on infarct size. They reflect the influence of defective cardiac pumping on the kidney, liver, brain and endothelium. Massive infarcts are accompanied by an increase in circulating renin and in renal renin content, by a decrease in angiotensinogen due to its consumption by renin, and to its insufficient hepatic synthesis, and by an increase in vasopressin secretion and biosynthesis in the hypothalamus. Converting enzyme inhibition has beneficial effect in this model by lowering cardiac load. It reduces arterial pressure, reverses bi-atrial and right ventricular hypertrophy, reduces the changes in the myosin isoenzyme patterns, and normalizes subendocardial fibrosis and the level of ANF. Although the effects of converting enzyme inhibition are beneficial in this model, they are restricted by their inability to normalize the load and stress when the initial loss of cardiac contractile material exceeds 40%.

Topics: Angiotensin-Converting Enzyme Inhibitors; Angiotensinogen; Animals; Atrial Natriuretic Factor; Collagen; Cyclic GMP; Hypertrophy, Left Ventricular; Indoles; Isoenzymes; Kidney; Myocardial Infarction; Myocardium; Myosins; Perindopril; Rats; Rats, Wistar; Renin; Vasopressins; Ventricular Dysfunction, Left